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Post-Doctoral Fellowships
Molecular Epidemiology of Lung Function: An Integrated Approach
Chronic obstructive pulmonary disease (COPD) poses a heavy morbidity and mortality burden on
both individual patients and society. In its severe stages, it is associatedwith functional impairment,
reduced quality of life, recurrent exacerbations, systemic manifestations and increased mortality
risk. Recently, it has been established that once the disease has occurred, patients with COPD
have increased levels of both airway and systemic inflammation and that the intensity of systemic
inflammation correlates with the severity of the disease. However, it remains unknown whether
levels of systemic inflammation can identify smokers at risk of COPD during their young to middle
adult life, how inflammatory markers interact with molecules involved in other pathogenetic
pathways, and whether integration of information from multiple biomarkers and from variation in
their encoding genes can improve their predictive value on decline of lung function.
The project’s main objective was to identify systemic biomarkers of decline of lung function using
the Spanish branch of the prospective population-based European Community Respiratory Health
Survey (ECRHS). We tested 20 biomarkers in serum, variably involved in inflammation, innate
immunity, proteolysis, oxidative stress, auto-immune responses and other potential pathways. A
large group of candidate genes related to the above biomarkers was also genotyped. A complete
screening of all measured biomarkers against concomitant lung function levels has been completed.
Screening of all genotyped single nucleotide polymorphisms (SNPs) against biomarkers levels
resulted in multiple significant associations, suggesting that many of these proteins are under
significant genetic control. The aim to determine whether the above associations are different in
smokers as comparedwith non-smokers and in asthmatics versus non-asthmatics has been achieved.
This was achieved by stratified analyses in which biomarkers were related to concomitant levels
and subsequent decline of lung function in these different groups separately. With some notable
exceptions, most associations did not differ across these groups. Large amounts of molecular
data have been produced and will benefit future studies. For example, now that prospective data
for the third survey are available, we hope temporal sequence between biomarkers and clinical
phenotypes could be resolved and these data can be used to generate models of risk prediction.
Research publications
(1)
Guerra, S., Halonen, M., Sherrill, D.L., Venker, C., Spangenberg, A., Carsin, A.E., Tarès, L., Lavi, I., Barreiro,
E., Martínez-Moratalla, J., Urrutia, I., Sunyer, J., Antó, J.M., & Martinez, F.D. (2013). The relation of circulating
YKL-40 to levels and decline of lung function in adult life.
Respiratory Medicine, 107
(12), 1923-1930.
(2)
Rava, M., Tares, L., Lavi, I., Barreiro, E., Zock, J.P., Ferrer, A., Muniozguren, N., Nadif, R., Cazzoletti, L.,
Kauffmann, F., Anto, J.M., & Guerra, S. (2013). Serum levels of Clara cell secretory protein, asthma, and lung
function in the adult general population.
Journal of Allergy and Clinical Immunology, 132
(1), 230-232.
(3)
Gascon, M., Sunyer, J., Martínez, D., Guerra, S., Lavi, I., Torrent, M., & Vrijheid, M. (2014). Persistent organic
pollutants and children's respiratory health: The role of cytokines and inflammatory biomarkers.
Environment
International, 69
, 133-40.
Fellow
Iris Lavi
Centre for Research
in Environmental
Epidemiology,
CREAL, Spain
Supervisor
Stefano Guerra
2010-2012